10-deacetyl baccatin-III(10-DAB) is a very important precursor for the synthesis of paclitaxel and docetaxel analogues, which show excellent cytotoxicity against human ovaries, lungs, colon and breast cancer cell lines [ref. J. Med. chem. 1977, 40, 267-278].
10-deacetyl baccatin-III is represented by the following structural formula: ##STR1##
The compound 10-deacetyl baccatin-III is primarily found in the trunk and leaves of the plants of Taxus sp. in highest concentration. While the other parts of the plants also contain this compound, however, the concentration is less.
Most common methods of isolation of 10-DAB involves the extraction of biomass with alcohol or any protic solvent to yield an extract which is semipurified by solvent partition/maceration and finally selective crystallization or chromatography to yield 10-DAB. Some of the common methods employed in the art for extraction of 10-DAB are given herein below:
U.S. Pat. No. 5,393,895 relates to extracting the biomass with aliphatic alcohol followed by dilution with water and separating the insolubles. Thereafter, removing the total alcohol to yield an aqueous solution which is subjected to partition with organic solvents and selective crystallization to yield 10-DAB.
U.S. Pat. No. 5,736,366 relates to a process for obtaining 10-deacetyl baccatin-III. This process relates to extracting the biomass with water followed by adsorption on an appropriate substrate and desorbing using an organic solvent and finally deploying selective crystallization.
U.S. Pat. No. 5,453,521 relates to treating the biomass with aliphatic alcoholic and diluting with water, separating the insolubles from the hydroalcoholic solution and thereafter, removing the alcohol completely and extracting the aqueous solution with organic solvent followed by selective crystallization to obtain 10-DAB.
U.S. Pat. No. 5,393,896 relates to treating the biomass with water followed by treatment with organic solvent of the aqueous extract, the organic phase is further subjected to selective crystallization to yield 10-DAB.
WO 94/07881 relates to extraction of the biomass with water and thereafter adsorbing on a suitable substrate or without absorbing, and then treating with organic solvent, followed by selective crystallization to obtain 10-DAB.
WO 94/07882 relates to extraction of the biomass with methanol and followed by dilution with water, removing insolubles. The soluble portion is subjected to remove of alcohol totally to yield an aqueous solution which is subjected to partition with suitable organic solvent followed by selective crystallization to yield 10-DAB.
None of the above prior arts teach the isolation of paclitaxel present in the biomass, which is an important drug for the treatment of overian and breast cancer. In addition, the above processes do not lead to the complete separation of paclitaxel from 10-DAB, which is present in the primary extract. Further, the present invention provides a most economically and eco-friently process to isolate 10-DAB from Taxus species.